We are examining the basic mechanisms by which CNS lesions produce neurochemical changes in the remaining portions of brain and to relate these neurochemical changes to changes in the animal's behavior or sensitivity to various centrally acting drugs. More specifically, we are attempting to further map out the serotonergic, noradrenergic, dopaminergic, and cholinergic pathways in brain. We are also further examining the pathways that appear to contain neurons with high concentrations of aspartic and glutamic acid. We have found certain instances in which interruption of specific monoaminergic pathways are associated with specific changes in behavior, as for example, aphagia and adipsia following interruption of dopaminergic fibers to the neostriatum, hyperdipsia after interruption of cholinergic fibers from the septum, and increased pain sensitivity following interruption of serotonergic fibers to the telencephalon. In the latter instance, the behavioral effects of interrupting the serotonergic system could be reversed by administration of 5-hydroxytryptophan, the immediate precursor of serotonin. We have also established a procedure for measurement of evoked potentials of olfactory cortex in vitro and are examining the synaptic transmitters involved as well as the effects of drugs on transmission. The major purpose of these studies is to gain further knowledge of the manner in which behavioral effects of brain damage can be reversed by chemical means. BIBLIOGRAPHIC REFERENCES: Scholfield, C. N., & Harvey, J. A. Local anesthetics and barbiturates: Effects on evoked potentials in isolated mammalian cortex. Journal of Pharmacology and Experimental Therapeutics, 1976, 195, 522-531. Yunger, L. M., & Harvey, J. A. Behavioral effects of L-5-hydroxytryptophan after destruction of ascending serotonergic pathways in rats: Evidence for a role of catecholaminergic neurons. Journal of Pharmacology and Experimental Therapeutics, 1976, 196, 307-315.